Protective effects of total flavonoids of Astragalus membranaceus Bunge combined with selenium-enriched yeast against zearalenone-induced reproductive injury in male mice

Zearalenone (ZEA) is an environmental endocrine disruptor generated by fungi, which mainly causes reproductive injury. Total flavonoids of Astragalus membranaceus Bunge (TFA) is one of the most beneficial components of Astragalus membranaceus Bunge with a variety of pharmacological effects, selenium (Se) is a trace element with antioxidant effect, but it remains unclear whether their combination can control the reproductive toxicity caused by ZEA. This study aims to determine the effects and potential mechanisms of TFA combined with Se-enriched yeast (SeY) against ZEA-induced reproductive injury in male mice. In this study, we first utilized network pharmacology to predict the possible targets of TFA combined with SeY, and further elucidated and verified the effects and underlying mechanisms through in vivo experiment. Network pharmacology showed that the core targets of TFA combined with SeY against testicular damage were closely related to inflammation, oxidative stress and apoptosis. In vivo experiment demonstrated that TFA combined with SeY effectively improved sperm quality, alleviated pathological changes of testis, and repaired mitochondrial damage and blood-testis barrier. Moreover, TFA combined with SeY reduced ZEA-induced inflammation through suppressing the overproduction of inflammatory factors, attenuated oxidative stress through activating Keap1/Nrf2/HO-1 pathway, and mitigated apoptosis through inhibiting mitochondrial and death receptor pathways. In conclusion, TFA combined with SeY exerted protective effects against ZEA-induced testicular injury by anti-inflammatory, antioxidant and anti-apoptotic mechanisms. This offers a promising solution for controlling ZEA poisoning and provides experimental support for the combined use of traditional Chinese medicine and trace elements.